title: Cell type-specific alterations in the nucleus accumbens by repeated exposures to cocaine.
abstract: BACKGROUND
  The nucleus accumbens (NAc) is a brain region critically involved in psychostimulant-induced neuroadaptations. A major proportion of NAc neurons consists of medium spiny neurons (MSNs), commonly divided into two major subsets on the basis of their expression of D1 dopamine receptors (D1R-MSNs) or D2 dopamine receptors (D2R-MSNs). Although NAc MSNs are known to undergo extensive alterations in their characteristics upon exposure to drugs of abuse, the functional and structural changes specific to each type of MSN have yet to be fully resolved.
  
  
  METHODS
  We repeatedly injected cocaine into transgenic mice expressing enhanced green fluorescent protein under the control of promoters for either D1R or D2R and then analyzed the physiological characteristics of each type of MSN by whole-cell recording. We also analyzed cocaine-induced changes of spine densities of individual MSNs with recombinant lentivirus in a cell type-specific manner and corroborated findings by use of a pathway-specific labeling using recombinant rabies virus.
  
  
  RESULTS
  The D1R-MSNs exhibited decreased membrane excitability but increased frequency of miniature excitatory postsynaptic currents after repeated cocaine administration, whereas D2R-MSNs displayed a decrease in miniature excitatory postsynaptic current frequency with no change in excitability. Interestingly, miniature inhibitory postsynaptic currents decreased in D1R-MSNs but were unaffected in D2R-MSNs. Moreover, morphological analyses revealed a selective increase in spine density in D1R-MSNs after chronic cocaine exposure.
  
  
  CONCLUSIONS
  This study provides the first experimental evidence that NAc MSNs differentially contribute to psychostimulant-induced neuroadaptations by changing their intrinsic, synaptic, and structural characteristics in a cell type-specific fashion.
authors.affiliation: Department of Life Science, Pohang University of Science and Technology, Pohang, Gyungbuk, Republic of Korea.
authors.forename: Juhyun
authors.initials: J
authors.lastname: Kim
authors.forename: Bong-Hyun
authors.initials: BH
authors.lastname: Park
authors.forename: Joo Han
authors.initials: JH
authors.lastname: Lee
authors.forename: Sang Ki
authors.initials: SK
authors.lastname: Park
authors.forename: Joung-Hun
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000818:Animals; D003042:Cocaine / Q000008:administration & dosage*; D049229:Dendritic Spines / Q000187:drug effects / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D055369:Miniature Postsynaptic Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D018765:Dopamine Uptake Inhibitors; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D003042:Cocaine